tbuckley/cabot-search huggingface dataset:
The National Clinical Care Commission Report to Congress: Leveraging Federal Policies and Programs for Population-Level Diabetes Prevention and Control: Recommendations From the National Clinical Care Commission
Authors: Dean Schillinger, Ann Bullock, Clydette Powell, Naomi K. Fukagawa, M. Carol Greenlee, Jana Towne, Jasmine D. Gonzalvo, Aaron M. Lopata, J. William Cook, William H. Herman
Journal: Diabetes Care (2023)

The etiology of type 2 diabetes is rooted in a myriad of factors and exposures at individual, community, and societal levels, many of which also affect the control of type 1 and type 2 diabetes. Not only do such factors impact risk and treatment at the time of diagnosis but they also can accumulate biologically from preconception, in utero, and across the life course. These factors include inadequate nutritional quality, poor access to physical activity resources, chronic stress (e.g., adverse childhood experiences, racism, and poverty), and exposures to environmental toxins. The National Clinical Care Commission (NCCC) concluded that the diabetes epidemic cannot be treated solely as a biomedical problem but must also be treated as a societal problem that requires an all-of-government approach. The NCCC determined that it is critical to design, leverage, and coordinate federal policies and programs to foster social and environmental conditions that facilitate the prevention and treatment of diabetes. This article reviews the rationale, scientific evidence base, and content of the NCCC's population-wide recommendations that address food systems; consumption of water over sugar-sweetened beverages; food and beverage labeling; marketing and advertising; workplace, ambient, and built environments; and research. Recommendations relate to specific federal policies, programs, agencies, and departments, including the U.S. Department of Agriculture, the Food and Drug Administration, the Federal Trade Commission, the Department of Housing and Urban Development, the Environmental Protection Agency, and others. These population-level recommendations are transformative. By recommending health-in-all-policies and an equity-based approach to governance, the NCCC Report to Congress has the potential to contribute to meaningful change across the diabetes continuum and beyond. Adopting these recommendations could significantly reduce diabetes incidence, complications, costs, and inequities. Substantial political resolve will be needed to translate recommendations into policy. Engagement by diverse members of the diabetes stakeholder community will be critical to such efforts.
Comparative Risk of Angioedema With Sacubitril-Valsartan vs Renin-Angiotensin-Aldosterone Inhibitors
Authors: Efe Eworuke, Emily C. Welch, Nicole Haug, Casie Horgan, Hye Seung Lee, Yueqin Zhao, Ting-Ying Huang
Journal: Journal of the American College of Cardiology (2023)
Abnormal Platelet Counts and Clonal Hematopoiesis in the General Population
Authors: Priscilla Kamphuis, Maaike G.J.M. van Bergen, Isabelle A. van Zeventer, Aniek O. de Graaf, Avinash G. Dinmohamed, Jonas B. Salzbrunn, Jan Jacob Schuringa, Bert A. van der Reijden, Gerwin Huls, Joop H. Jansen
Journal: HemaSphere (2023)

Clonal hematopoiesis (CH) is defined by the presence of somatic mutations that may cause clonal expansion of hematopoietic cells. Here, we investigated the association between platelet count abnormalities, CH and consequences on overall survival and the development of hematological malignancies. Individuals with thrombocytopenia (n = 631) or thrombocytosis (n = 178) ≥60 years, and their age- and sex-matched controls, were selected within the population-based Lifelines cohort (n = 167,729). Although the prevalence of CH was not increased in thrombocytopenia cases compared with their controls (37.9% vs 39.3%; P = 0.639), mutations in spliceosome genes ( SF3B1 , SRSF2 , U2AF1 ) were significantly enriched in thrombocytopenia cases ( P = 0.007). Overall, CH in combination with thrombocytopenia did not impact on survival, but thrombocytopenia in combination with multiple mutated genes (hazard ratio [HR] = 2.08, 95% confidence interval [CI], 1.24-3.50; P = 0.006), mutations in TP53 (HR = 5.83, 95% CI, 2.49-13.64; P &lt; 0.001) or spliceosome genes (HR = 2.69, 95% CI, 1.29-5.63; P = 0.009) increased the risk of death. The prevalence of CH in thrombocytosis cases was higher compared with controls (55.8% vs 37.7%; P &lt; 0.001). Especially mutations in JAK2 ( P &lt; 0.001) and CALR ( P = 0.003) were enriched in individuals with thrombocytosis. The presence of CH in individuals with thrombocytosis did not impact on overall survival. However, during follow-up of 11 years 23% of the individuals with thrombocytosis and CH were diagnosed with hematological malignancies. From these, 81% were diagnosed with myeloproliferative disease and 76% carried driver mutations JAK2 , CALR , or MPL .
Minimal invasiveness in vertical ridge augmentation
Authors: Istvan Urban, Eduardo Montero, Ignacio Sanz‐Sánchez, David Palombo, Alberto Monje, Grazia Tommasato, Matteo Chiapasco
Journal: Periodontology 2000 (2023)

Abstract Vertical ridge augmentation is one of the most challenging procedures in implant dentistry because of the advanced skills required by the operator and the fact that bone augmentation is aimed outside the bony contour, in an environment of reduced blood supply. What is more, the flap management required to ensure soft tissue closure frequently leads to associated comorbidities in terms of swelling and hematomas. For these reasons, and even if autologous onlay block grafts are still the gold standard, new techniques and biomaterials have favored the development of potentially less invasive approaches. The present work evaluates the most recent strategies in vertical ridge augmentation to reduce invasiveness and complications, including diagnostic/treatment planning considerations, surgical techniques, digital tools (eg, customized titanium meshes/membranes or bone blocks), and future trends in the field of tissue engineering and cell therapy.
Combination treatment of mannose and GalNAc conjugated small interfering RNA protects against lethal Marburg virus infection
Authors: Xin Ye, Richard Holland, Mark Wood, Chris Pasetka, Lorne Palmer, Eleni Samaridou, Kevin McClintock, Viktoriya Borisevich, Thomas W. Geisbert, Robert W. Cross, James Heyes
Journal: Molecular Therapy (2023)

(Molecular Therapy 31, 269–281; January 2023) In the originally published version of this article, Figure S9 was included with an error. Incorrect images were copied to the fluorescent microscopic images for the 5 ug/mL Cy3-tetra-mannose-siCD45 and 5 ug/mL Cy3-tetra-GalNAc-siCD45 treated samples. This error has been corrected online with the inclusion of the correct images. The authors sincerely apologize for this error.Figure S9 (original)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Combination treatment of mannose and GalNAc conjugated small interfering RNA protects against lethal Marburg virus infectionYe et al.Molecular TherapySeptember 15, 2022In BriefMARV infection causes high mortalities, and effective treatments are in pressing need. We established a hexavalent mannose ligand conjugate platform that successfully delivered siRNAs to macrophages and dendritic cells. Combination of this mannose-siRNA alongside our hepatocyte-targeting GalNAc-siRNA conjugate provided full protection against MARV infection in guinea pigs. Full-Text PDF Open Access
Gut microbial metabolite hyodeoxycholic acid targets the TLR4/MD2 complex to attenuate inflammation and protect against sepsis
Authors: Jiaxin Li, Yuqi Chen, Rui Li, Xianglong Zhang, Tao Chen, Fengyi Mei, Ruofan Liu, Meiling Chen, Yue Ge, Hongbin Hu, Rongjuan Wei, Zhenfeng Chen, Hongying Fan, Zhenhua Zeng, Yongqiang Deng, Haihua Luo, Shuiwang Hu, Shumin Cai, Feng Wu, Nengxian Shi, Zhang Wang, Yunong Zeng, Ming Xie, Yong Jiang, Zhongqing Chen, Wei Jia, Peng Chen
Journal: Molecular Therapy (2023)
SARS-CoV-2 Antibody Responses to the Ancestral SARS-CoV-2 Strain and Omicron BA.1 and BA.4/BA.5 Variants in Nursing Home Residents After Receipt of Bivalent COVID-19 Vaccine — Ohio and Rhode Island, September–November 2022
Authors: David H. Canaday, Oladayo A. Oyebanji, Elizabeth M. White, Jürgen Bosch, Clare Nugent, Igor Vishnepolskiy, Yasin Abul, Elise M. Didion, Alexandra Paxitzis, Nicholas Sundheimer, Vaishnavi Ragavapuram, Dennis Wilk, Debbie Keresztesy, Yi Cao, Kerri St. Denis, Kevin W. McConeghy, L. Clifford McDonald, John A. Jernigan, Eleftherios Mylonakis, Brigid M. Wilson, Christopher L. King, Alejandro B. Balazs, Stefan Gravenstein
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Introduction of monovalent COVID-19 mRNA vaccines in late 2020 helped to mitigate disproportionate COVID-19-related morbidity and mortality in U.S. nursing homes (1); however, reduced effectiveness of monovalent vaccines during the period of Omicron variant predominance led to recommendations for booster doses with bivalent COVID-19 mRNA vaccines that include an Omicron BA.4/BA.5 spike protein component to broaden immune response and improve vaccine effectiveness against circulating Omicron variants (2). Recent studies suggest that bivalent booster doses provide substantial additional protection against SARS-CoV-2 infection and severe COVID-19-associated disease among immunocompetent adults who previously received only monovalent vaccines (3).* The immunologic response after receipt of bivalent boosters among nursing home residents, who often mount poor immunologic responses to vaccines, remains unknown. Serial testing of anti-spike protein antibody binding and neutralizing antibody titers in serum collected from 233 long-stay nursing home residents from the time of their primary vaccination series and including any subsequent booster doses, including the bivalent vaccine, was performed. The bivalent COVID-19 mRNA vaccine substantially increased anti-spike and neutralizing antibody titers against Omicron sublineages, including BA.1 and BA.4/BA.5, irrespective of previous SARS-CoV-2 infection or previous receipt of 1 or 2 booster doses. These data, in combination with evidence of low uptake of bivalent booster vaccination among residents and staff members in nursing homes (4), support the recommendation that nursing home residents and staff members receive a bivalent COVID-19 booster dose to reduce associated morbidity and mortality (2).
Scale-Up of HIV Antiretroviral Therapy and Estimation of Averted Infections and HIV-Related Deaths — Uganda, 2004–2022
Authors: Emilio Dirlikov, Joseph Kamoga, Stella Alamo Talisuna, Jennifer Namusobya, Daniel E. Kasozi, Juliet Akao, Estella Birabwa, Jennifer A. Ward, Bill Elur, Ray W. Shiraishi, Carl Corcoran, Vamsi Vasireddy, Richard Nelson, Lisa J. Nelson, Mary Borgman, Eleanor Namusoke Magongo, Linda Nabitaka Kisaakye, Cordelia Katureebe, Wilford Kirungi, Joshua Musinguzi, Natalie E. Brown, Daniel Bogere, Jessica T. Conley, Arthur G. Fitzmaurice, Jennifer S. Galbraith, Joseph Kabanda, Geoffrey Kabuye, Julius N. Kalamya, Charles Kavuma, Herbert S. Kiyingi, Deus Lukoye, Stephen Malinzi, Lisa A. Mills, Kenneth Musenge, Diriisa Musisi, Kenneth Mwambi, Christina W. Mwangi, Grace A. Namayanja, Phoebe M. Namukanja, Sophie Nantume, Pamela Nasirumbi Muniina, Esther R. Nazziwa, Thomas Nsibambi, Thomas Nsibambi, Jonathan Ntale, Robert Ochai, Samuel Sendagala, Alfred S. Lutaaya, Hardson K. Tibihenda, Rachel K. Kwezi, Jaffer Byawaka Majugu, Jacqueline Calnan, Immaculate N. Ddumba, Seyoum Dejene, Bikokye W. Kafeero, Garoma Kena, Dalsone Kwarisiima, Sheila Kyobutungi, Haruna Lule, Ismail Mbabali, Norbert Mubiru, Emmanuel Mugisa, Miriam Murungi, Aleathea D. Musah, Suzan K. Nakawunde, Victoria Nakiganda, Jennifer Namusobya, Saidah Nankabirwa, Peter Niwagaba, Esther K. Nkolo, Tamara Nsubuga-Nyombi, Babatunji Odelola
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

On January 28, 2003, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the largest commitment by any nation to address a single disease in history, was announced.* In April 2004, the first person in the world to receive PEPFAR-supported antiretroviral therapy (ART) was a man aged 34 years in Uganda. Effective ART reduces morbidity and mortality among persons with HIV infection (1) and prevents both mother-to-child transmission (MTCT) (2) and sexual transmission once viral load is suppressed to undetectable levels (<200 viral copies/mL) (3). By September 2022, more than 1.3 million persons with HIV infection in Uganda were receiving PEPFAR-supported ART, an increase of approximately 5,000% from September 2004. As indicators of the ART program's effectiveness, a proxy MTCT rate decreased 77%, from 6.4% in 2010 to 1.5% in 2022, and the viral load suppression rate (<1,000 viral copies/mL) increased 3%, from 91% in 2016 to 94% in September 2022. During 2004-2022, ART scale-up helped avert nearly 500,000 HIV infections, including more than 230,000 infections among HIV-exposed infants, and approximately 600,000 HIV-related deaths. Going forward, efforts will focus on identifying all persons with HIV infection and rapidly linking them to effective ART. PEPFAR remains committed to continued strong partnership with the Government of Uganda, civil society, and other development partners toward sustainable solutions aligned with the Joint United Nations Programme on HIV/AIDS (UNAIDS) fast-track strategy to ending the global AIDS epidemic by 2030† and safeguarding impact achieved in the long term.
Blocking Genomic Instability Prevents Acquired Resistance to MAPK Inhibitor Therapy in Melanoma
Authors: Prashanthi Dharanipragada, Xiao Zhang, Sixue Liu, Shirley H. Lomeli, Aayoung Hong, Yan Wang, Zhentao Yang, Kara Z. Lo, Agustin Vega-Crespo, Antoni Ribas, Stergios J. Moschos, Gatien Moriceau, Roger S. Lo
Journal: Cancer Discovery (2023)

Blocking cancer genomic instability may prevent tumor diversification and escape from therapies. We show that, after MAPK inhibitor (MAPKi) therapy in patients and mice bearing patient-derived xenografts (PDX), acquired resistant genomes of metastatic cutaneous melanoma specifically amplify resistance-driver, nonhomologous end-joining (NHEJ), and homologous recombination repair (HRR) genes via complex genomic rearrangements (CGR) and extrachromosomal DNAs (ecDNA). Almost all sensitive and acquired-resistant genomes harbor pervasive chromothriptic regions with disproportionately high mutational burdens and significant overlaps with ecDNA and CGR spans. Recurrently, somatic mutations within ecDNA and CGR amplicons enrich for HRR signatures, particularly within acquired resistant tumors. Regardless of sensitivity or resistance, breakpoint-junctional sequence analysis suggests NHEJ as critical to double-stranded DNA break repair underlying CGR and ecDNA formation. In human melanoma cell lines and PDXs, NHEJ targeting by a DNA-PKCS inhibitor prevents/delays acquired MAPKi resistance by reducing the size of ecDNAs and CGRs early on combination treatment. Thus, targeting the causes of genomic instability prevents acquired resistance. Acquired resistance often results in heterogeneous, redundant survival mechanisms, which challenge strategies aimed at reversing resistance. Acquired-resistant melanomas recurrently evolve resistance-driving and resistance-specific amplicons via ecDNAs and CGRs, thereby nominating chromothripsis-ecDNA-CGR biogenesis as a resistance-preventive target. Specifically, targeting DNA-PKCS/NHEJ prevents resistance by suppressing ecDNA/CGR rearrangements in MAPKi-treated melanomas. This article is highlighted in the In This Issue feature, p. 799.
Shedding Light on PARP Inhibitor Response through Functional Imaging
Authors: Ying L. Liu, Dmitriy Zamarin
Journal: Clinical Cancer Research (2023)

Summary Functional PET imaging using a PARP inhibitor (PARPi) analog may serve as an early, dynamic biomarker of response to PARPi therapy in high-grade serous ovarian cancer. Clinically, this could help to rapidly identify PARPi nonresponders, thereby maximizing efficacy and avoiding toxicities of futile treatments. See related article by Pantel et al., p. 1515
Letter to the editor: Importance of considering high-risk behaviours in COVID-19 vaccine effectiveness estimates with observational studies
Authors: Takeshi Arashiro, Yuzo Arima, Jin Kuramochi, Hirokazu Muraoka, Akihiro Sato, Kumi Chubachi, Kunihiro Oba, Atsushi Yanai, Hiroko Arioka, Yuki Uehara, Genei Ihara, Yasuyuki Kato, Naoki Yanagisawa, Yoshito Nagura, Hideki Yanai, Akihiro Ueda, Akira Numata, Hideaki Kato, Hideaki Oka, Yusuke Nishida, Takao Ooki, Yuki Nidaira, Ashley Stucky, Tadaki Suzuki, Chris Smith, Martin Hibberd, Koya Ariyoshi, Motoi Suzuki
Journal: Eurosurveillance (2023)

Preview this article: Letter to the editor: Importance of considering high-risk behaviours in COVID-19 vaccine effectiveness estimates with observational studies, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/28/4/eurosurv-28-4-4-1.gif
Pathogen-specific T Cells: Targeting Old Enemies and New Invaders in Transplantation and Beyond
Authors: Anastasia Papadopoulou, Maria Alvanou, George Karavalakis, Ifigeneia Tzannou, Evangelia Yannaki
Journal: HemaSphere (2023)

Adoptive immunotherapy with virus-specific cytotoxic T cells (VSTs) has evolved over the last three decades as a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after solid organ or allogeneic hematopoietic cell-transplantation (allo-HCT). Since the early proof-of-principle studies demonstrating that seropositive donor-derived T cells, specific for the commonest pathogens post transplantation, namely cytomegalovirus or Epstein-Barr virus (EBV) and generated by time- and labor-intensive protocols, could effectively control viral infections, major breakthroughs have then streamlined the manufacturing process of pathogen-specific T cells (pSTs), broadened the breadth of target recognition to even include novel emerging pathogens and enabled off-the-shelf administration or pathogen-naive donor pST production. We herein review the journey of evolution of adoptive immunotherapy with nonengineered, natural pSTs against infections and virus-associated malignancies in the transplant setting and briefly touch upon recent achievements using pSTs outside this context.
Outcome Prediction in Patients With Large B-cell Lymphoma Undergoing Chimeric Antigen Receptor T-cell Therapy
Authors: Conrad-Amadeus Voltin, Philipp Gödel, Laura Beckmann, Jan-Michel Heger, Carsten Kobe, Nadine Kutsch, Peter Borchmann, Markus Dietlein, Ken Herrmann, Matthias Stelljes, Kambiz Rahbar, Georg Lenz, H. Christian Reinhardt, Marcel Teichert, Richard Noppeney, Jörn C. Albring, Robert Seifert, Bastian von Tresckow, Sarah Flossdorf, Christine Hanoun
Journal: HemaSphere (2023)

The introduction of chimeric antigen receptor (CAR) T-cell therapy has led to a fundamental shift in the management of relapsed and refractory large B-cell lymphoma. However, our understanding of risk factors associated with non-response is still insufficient and the search for predictive biomarkers continues. Some parameters measurable on 18 F-fluorodeoxyglucose positron emission tomography (PET) may be of additional value in this context. A total of 47 individuals from three German university centers who underwent re-staging with PET prior to CAR T-cell therapy were enrolled into the present study. After multivariable analysis considering tumor characteristics and patient factors that might affect progression-free survival (PFS), we investigated whether metabolic tumor volume (MTV) or maximum standardized uptake value (SUV max ) further improve risk stratification. Their most suitable cut-offs were determined by Cox and logistic regression. Forward selection identified extra-nodal disease as the most predictive factor of those routinely available, and we found it to be associated with significantly inferior overall survival after CAR T-cell treatment ( P = 0.012). Furthermore, patients with MTV and SUV max higher than the optimal threshold of 11 mL and 16.7, respectively, experienced shorter PFS ( P = 0.016 and 0.002, respectively). Hence, these risk factors might be useful for selection of individuals likely to benefit from CAR T-cell therapy and their management.
Reduced 8-Gray Compared to Standard 12-Gray Total Body Irradiation for Allogeneic Transplantation in First Remission Acute Lymphoblastic Leukemia: A Study of the Acute Leukemia Working Party of the EBMT
Authors: Alexandros Spyridonidis, Myriam Labopin, Bipin Savani, Sebastian Giebel, Gesine Bug, Stefan Schönland, Nicolaus Kröger, Matthias Stelljes, Thomas Schroeder, Andrew McDonald, Igor-Wolfgang Blau, Martin Bornhäuser, Montse Rovira, Wolfgang Bethge, Andreas Neubauer, Arnold Ganser, Jean Henri Bourhis, Matthias Edinger, Bruno Lioure, Gerald Wulf, Kerstin Schäfer-Eckart, Mutlu Arat, Zinaida Peric, Christoph Schmid, Ali Bazarbachi, Fabio Ciceri, Arnon Nagler, Mohamad Mohty
Journal: HemaSphere (2023)

In this registry-based study, we compared outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) in adult patients with acute lymphoblastic leukemia (ALL) transplanted in first complete remission (CR-1), following conditioning with total body irradiation (TBI) at a standard 12-Gray or at a lower 8-Gray total dose. Patients received fludarabine (flu) as the sole chemotherapy complementing TBI. Eight-Gray TBI/flu was used in 494 patients and 12-Gray TBI/flu in 145 patients. Eighty-eight (23.1%) and 36 (29%) of the patients had Ph-negative B-ALL, 222 (58.3%) and 53 (42.7%) had Ph-positive B-ALL, 71 (18.6%) and 35 (28.2%) T-ALL, respectively ( P = 0.008). Patients treated with 8-Gray were older than ones received 12-Gray (median 55.7 versus 40.3 years, P &lt; 0.0001) and were more frequently administered in vivo T-cell depletion (71% versus 40%, P &lt;0.0001). In a multivariate model adjusted for age, type of ALL, and other prognostic factors, leukemia-free survival (primary endpoint) as well as relapse, nonrelapse mortality, overall survival, and GVHD-free, relapse-free survival were not influenced by the TBI dose. These results were confirmed when we focused on patients &lt;55 years of age (median 47 years). Patients with Ph-positive ALL or T-ALL had significantly better survival outcomes than ones with Ph-negative B-ALL, mainly due to significantly fewer relapses. We conclude that 8-Gray TBI is sufficient for adult patients with ALL transplanted in CR-1 with no additional benefit of augmenting the conditioning intensity to 12-Gray.
Revascularization Strategies for Patients With Femoropopliteal Peripheral Artery Disease
Authors: Serdar Farhan, Florian K. Enzmann, Patrick Bjorkman, Haroon Kamran, Zhongjie Zhang, Samantha Sartori, Birgit Vogel, Arthur Tarricone, Klaus Linni, Maarit Venermo, Daphne van der Veen, Herve Moussalli, Roxana Mehran, Michel M.P.J. Reijnen, Marc Bosiers, Prakash Krishnan
Journal: Journal of the American College of Cardiology (2023)
The Burden of Surviving Childhood Medulloblastoma: A Population-Based, Matched Cohort Study in Ontario, Canada
Authors: Hallie Coltin, Priscila Pequeno, Ning Liu, Derek S. Tsang, Sumit Gupta, Michael D. Taylor, Eric Bouffet, Paul C. Nathan, Vijay Ramaswamy
Journal: Journal of Clinical Oncology (2023)

Survivors of childhood medulloblastoma suffer from substantial late effects. We characterized these sequelae using real-world health services data in a population-based cohort of medulloblastoma survivors.